Nostoc muscorum A is a species of cyanobacterium (blue green alga) whose life cycle has been extensively studied. The normal life cycle of the Nostoc muscorum A can be described as having the following stages which are illustrated in FIG. 1.
Stage 1 consists of the hormogone or motile trichome (mt) with tapered terminal cells (tc). In stage 2, the terminal cells begin differentiation to terminal heterocysts (th) and the intercalary cells enlarge. In stages 3 and 4, the intercalary cells continue to enlarge and form clusters while a gelatinous sheath forms around each of the clusters. In stage 5, the cells in each of the enclosed clusters align to form filaments (f). In stage 6, the newly formed filaments begin to form intercalary heterocysts (ih) (heterocystous filaments). In stage 7, the gelatinous sheath begins to break down. In stage 8, the filaments break at the intercalary heterocysts giving rise to hormogonia and heterocysts. In stage 9, the swarming (gliding) hormogonia may form spiral aggregates (sa) of the motile elements (called motile trichomes). When these stop moving, the life cycle then can repeat.
This life cycle can be affected by light and by growth medium composition. When Nostoc muscorum A is grown heterotrophically, in complete darkness, in a growth medium containing the sugars glucose or sucrose, the Nostoc strain grows in a coccoid form called the aseriate stage, which upon exposure to light differentiates synchronously to the filamentous stage. The filaments break, release their heterocysts and then further differentiate to form hormogonia.
However, if the growth culture contains glucose and the growth culture is incubated under cool-white fluorescent illumination, then the formation of hormogonia becomes progressively inhibited. As a result, the mature culture with glucose consists exclusively of long unbroken heterocystous filaments. The wooly appearance of this type of growth in culture is termed "lanose".
Additionally, if the lanose culture, grown in continuously shaken glucose-containing media under cool-white fluorescent light, is then exposed to red fluorescent light, the heterocystous filaments convert to motile hormogonia. Subsequently, if the hormogonial suspension is placed in unshaken vessels in cool-white fluorescent light, these hormogonia swarm on surfaces or in semi-solid media to form tight spiral aggregates of gliding motile trichomes. In addition, the liberation of the hormogonia produces free heterocysts, which display a high frequency of germination, if produced after growing in a culture containing Medium I and approximately 10.sup.-3 % proteose peptone in addition to glucose.
Plating out germinable heterocysts and picking individual microcolonies derived from single heterocysts allow for the routine isolation of various strains of Nostoc muscorum A which differ in their properties of hormogonial motility and aggregation.
Further, the mechanisms of red light induction and photo-reversal are non-photosynthetic. Very small amounts of light energy are required to induce filamentous development of the aseriate cells. Development occurs in darkness following short light exposures. Red-light quanta from the 650 nm region of the spectrum induce development and green-light quanta, approx. 500-590 nm, reverse the effects of red light exposure.
It has been further shown that the hormogonial aggregation is accomplished by the formation of sticky protuberant strands of mucilaginous material that hold the motile hormogonia together. Based on the specificity of substances that inhibit aggregation and observation by electron microscopy of the attachment fibers, it is believed that aggregation is dependent upon the synthesis of adhesins, consisting of externally secreted proteins, probably glycoproteins.
Moreover, microbiologists have come to believe that free-living and/or parasitic bacteria frequently attack a cell or organism by an initial attachment to that cell or organism. Therefore, it would be beneficial to prevent such attack by developing a new class of antibiotics which counteract the synthesis of bacterial adhesins responsible for the localization of bacterial pathogens at specific infection (attachment) sites. It is also believed that by blocking bacterial attachment to host cells/organisms the unattached bacteria are rendered more susceptible to the natural immune defenses of the body and to chemotherapeutic and/or prophylactic drug treatment.
Generally speaking, conventional screening methods for antibiotics focus on finding chemicals that are lethal or growth-inhibiting in action against the disease-causing organism. These screening methods employ techniques that detect the effectiveness of a chemical's action in affecting growth and viability of test organisms by mechanisms that include interference with cell wall formation, destruction of cellular membranes, and inhibition of biosynthesis or nutrient uptake. Therefore, conventional screening methods dependent upon inhibition of growth and viability are in that respect limited to the kinds of antibiotic producers that can be identified.